Clinical impact of routine esophagram after peroral endoscopic myotomy.

BACKGROUND AND AIMS: It is unclear whether the common practice of postoperative day (POD) 1 esophagram impacts clinical care or reliably identifies significant adverse events (AEs) related to peroral endoscopic myotomy (POEM). Therefore, we aimed to correlate the most clinically relevant esophagram findings with postoperative outcomes after POEM. METHODS: Patients were retrospectively reviewed and included if they underwent POEM at 1 of the 3 study institutions between 2014 and 2018. Patient outcomes were assessed in relation to relevant POD 1 esophagram findings such as esophageal dissection or leak. RESULTS: One hundred seventy post-POEM contrast esophagrams (139 fluoroscopy-based vs 31 CT-based) performed on POD 1 were included. Most esophagrams (n = 98) contained abnormal findings but only 5 showed esophageal leak or dissection. Confirmed postoperative AEs of leak or dissection occurred in 4 patients. In 2 patients, POD 1 esophagram appropriately identified the leak or dissection, but in the other 2 patients the initial esophagram was negative, and the AEs were not recognized before clinical deterioration. One patient had a false-positive leak and dissection noted on esophagram leading to an unremarkable endoscopy. CONCLUSIONS: Despite the low AE rate after POEM, follow-up esophagram on POD 1 frequently shows expected, unremarkable postprocedural findings and occasionally fails to diagnose serious AEs. This results in pitfalls in accuracy regarding agreement between esophagram versus clinical and endoscopic findings. Relying exclusively on esophagram for post-POEM clinical decision-making can lead to unnecessary additional testing or missed AEs.

Durability of pneumatic dilation monotherapy in treatment-naive achalasia patients.

BACKGROUND: Pneumatic dilation (PD) is often billed as a "short term" treatment for achalasia but anecdotally can last years. This study sought to explore how long a single pneumatic dilation may induce symptom remission in a treatment-naïve achalasia patient. METHODS: A single center, retrospective chart review of patients with an ICD-9 or - 10 code of achalasia between 2005 and 2017 was performed. Treatment naïve patients with manometric diagnosis of primary achalasia were included. Outcomes (success or failure); single vs multiple PD; age; and estimated duration of effect were evaluated. Each patient underwent a single PD unless re-intervention was required for relapse. RESULTS: 83 patients (52% female, median 51.6 ± 3.6 years) were included. 43% underwent 2 PD and 13% underwent 3 PD. There was no significant relation between age, gender, and number of PDs. After 1 PD, 87.5% of patients reported > 1 year of symptom remission. 80.5% of relapsed patients reported success after a 2nd dilation. 1 PD was more likely to result in success than multiple PDs (p < 0.001). The measured median duration of remission after 1 PD was 4.23 years, and for 2 PDs, 3.71 years. The median estimated remission time after 1 PD was 8.5 years (CI 7.3-9.7, p = 0.03). CONCLUSIONS: PD is a safe, durable treatment for achalasia. A single PD is likely to last years. A second PD, if required, also has a high likelihood of success.

Throat Clearing, Frequently Reported, But is it GERD Related?

GOALS: To identify the association of throat clearing (TC) with gastroesophageal reflux disease (GERD) during objective reflux monitoring in a large number of patients studied in our esophageal testing laboratory. BACKGROUND: TC is frequently reported and considered to be an atypical symptom of GERD. Atypical GERD symptoms have been widely investigated and empirically treated with proton pump inhibitors. STUDY: We reviewed ambulatory impedance-pH studies of 186 patients referred for evaluation of possible GERD from January 2011 to December 2015 to evaluate the symptom association (SA) of TC with both an abnormal number of reflux episodes and also abnormal esophageal acid exposure (EAE). Patients were divided into 2 groups; group 1: TC is the only reported symptom, group 2: TC is one of the symptoms. All patients were studied off proton pump inhibitors therapy. RESULTS: Group 1 where TC was the only symptom in 27/186 (14.5%) patients. There was no significant difference in positive SA between this group (6/27; 22%) and group 2 (43/159; 27%) (Z score P=0.59). There was also no significant association between SA and abnormal EAE whether TC was the only presenting symptom (χ, P=0.7) or one of the reported symptoms (χ, P=0.10). None of the 6/27 had abnormal EAE. CONCLUSION: Although TC is often considered a possible GERD-related symptom, we found a low probability of objective association. TC is not likely to be the only presenting symptom, and if it happens, it is unlikely to be associated with GERD. Perhaps, TC should not be considered as a GERD symptom, even as an atypical one.

Symptom Index or Symptom Association Probability?: A Closer Look at Symptom Association in Suspected GERD Patients.

BACKGROUND: Symptom index (SI) and symptom association probability (SAP) are popular methods used to measure symptom association in patients with gastroesophageal reflux disease (GERD). AIM: To investigate whether these 2 methods yield similar results in analysis of both typical and atypical GERD symptoms. MATERIALS AND METHODS: Combined impedance-pH reflux studies of 1471 patients tested for possible GERD symptoms from January 2010 to May 2015 were reviewed. SI and SAP were analyzed for typical and atypical GERD symptoms including heartburn, regurgitation, indigestion, chest pain, cough, and throat clearing (TC). Patients who reported <3 symptom events during the 24-hour monitoring period were excluded. ON and OFF proton pump inhibitor (PPI) groups were reviewed. Kappa coefficient (κ) rather than simple percentage was used to measure the agreement rate. Simple percentage agreement is a less reliable method compared with κ. RESULTS: On PPI therapy, there was a good κ between SI and SAP for regurgitation (0.68) and indigestion (0.64), moderate for heartburn (0.48) and chest pain (0.51), and poor for cough (0.33) and TC (0.29). There was a lower κ OFF PPI therapy for heartburn (0.36), regurgitation (0.44), and indigestion (0.50). But there was no difference in κ for chest pain (0.61), cough (0.29), and TC (0.33). CONCLUSIONS: SI and SAP showed better agreement for patients with typical GERD symptoms and even better when tested ON PPI. A better symptom association method is needed for patients with atypical GERD symptoms.

Characteristics of Consecutive Esophageal Motility Diagnoses After a Decade of Change.

BACKGROUND AND AIMS: Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) measures concomitantly bolus transit and pressure changes allowing determination of the functional impact of esophageal motility abnormalities. Ten years ago our laboratory reported MII-EM results in 350 consecutive patients. Since then high-resolution impedance manometry (HRIM) became available and the definitions of ineffective esophageal motility (IEM) and nutcracker esophagus were revised. The aim of this study was to assess the impact of these developments on esophageal function testing. METHODS: From August 2012 through May 2013, HRIM was performed in 350 patients referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. While taking advantage of the new technology and revised criteria, HRIM findings were classified according to the conventional criteria to allow more appropriate comparison with our earlier analysis. RESULTS: Compared with the study performed 10 years ago, the prevalence of normal manometry (36% vs. 35%), achalasia (7% vs. 8%), scleroderma (1% vs. 1%), hypertensive lower esophageal sphincter (LES) (7% vs. 7%), and hypotensive LES (1% vs. 2%) remained the same, whereas the prevalence of distal esophageal spasm (9% vs. 3%), nutcracker esophagus (9% vs. 3%), and poorly relaxing LES (10% vs. 3%) decreased and the prevalence of IEM increased (20% vs. 31%) significantly. Compared with the early study, normal liquid bolus transit was significantly different in patients with hypertensive LES (96% vs. 57%) and poorly relaxing LES (55% vs. 100%). CONCLUSIONS: This study brings to light the increase in prevalence of IEM. In addition, it suggests that the hypertensive LES and poorly relaxing LES may each affect bolus transit in about half of these patients.

Cough and Throat Clearing: Atypical GERD Symptoms or Not GERD at All?

GOALS: To investigate the frequency of throat clearing (TC) and cough and how often each is associated with a positive symptom index (SI) for reflux. BACKGROUND: Many patients referred to our esophageal laboratory for gastroesophageal reflux disease (GERD) evaluation have "atypical" or "extraesophageal" symptoms. STUDY: We reviewed ambulatory impedance-pH studies of 267 patients referred for evaluation of possible GERD symptoms from January 2012 to December 2013 to evaluate the frequency of cough, TC, and their association with an abnormal number of reflux episodes. Patients with <3 symptom events/24 hours were excluded. Additional analysis was done for those with ≥24 (excessive) symptoms of TC or cough/24 hours. Eighty percent of patients were tested on proton pump inhibitor therapy. SI for either or both symptoms was calculated. RESULTS: A total of 112 of 267 patients (42%) reported both TC and cough on study day, 76/267 (28%) cough without TC and 79/267 (30%) TC without cough. Only 9/112 (8%) had a positive SI, versus 20/76 (26%) and 17/79 (22%) for cough (P=0.0006) and TC (P=0.007), respectively.A total of 136 of 267 patients (51%) reported 3 to 23 TC events/24 hours; 27/136 (20%) had a positive SI. Fifty-five of 267 (27%) had "excessive" TC. Only 7/55 (13%) had a positive SI (P=0.24).A total of 142 of 267 patients (53%) reported 3 to 23 cough events/24 hours; 43/142 (30%) had a positive SI. Forty-six of 267 (17%) had "excessive" cough. Only 6/46 (13%) had a positive SI (P=0.02).Analyses based on ON/OFF therapy, also showed same low rate of positive test and significantly higher number of reflux episodes in those with positive SI. CONCLUSIONS: Although cough and TC are often considered possible GERD symptoms, there is a low probability of objective association. This is even less likely if both symptoms are present. Those patients who reported "excessive" cough are less likely to have a positive SI.

Concomitant Administration of a Histamine2 Receptor Antagonist and Proton Pump Inhibitor Enhances Gastric Acid Suppression.

STUDY OBJECTIVE: Because it has been hypothesized that histamine2 receptor antagonists (H2 RAs) might interfere with the action of proton pump inhibitors (PPIs) when the drugs are given concomitantly, we sought to compare the pharmacodynamic effects of simultaneous administration of a PPI and an H2 RA with the effects of each drug administered alone. DESIGN: Prospective, randomized, double-blind, three-way crossover study. SETTING: Esophageal motility laboratory at a large teaching hospital. SUBJECTS: Twenty-one healthy volunteers. INTERVENTION: Subjects were randomized to one of three treatment arms: an H2 RA (ranitidine 300 mg) plus placebo, a PPI (omeprazole 40 mg) plus placebo, or ranitidine 300 mg plus omeprazole 40 mg, all given once/day at 8 a.m., 30 minutes before a standard breakfast, for 1 week. The subjects then received the other two treatments, with each treatment period separated by a 1-week washout period. MEASUREMENTS AND MAIN RESULTS: The primary outcome was length of time that the gastric pH remained higher than 4. Secondary outcomes were median gastric pH higher than 4 and percentage of time that the gastric pH remained higher than 4. On day 7, ambulatory intragastric pH was recorded over an 8-hour period in each treatment arm. The combination of ranitidine and omeprazole resulted in a significantly longer time that the gastric pH remained higher than 4 (median 410.5 min [interquartile range (IQR) 298.5-454.25 min]) versus either omeprazole alone (median 356.7 min [IQR 254.9-419.2 min], p=0.023) or ranitidine alone (134.1 min [IQR 99.9-302.5 min], p<0.0001). Median gastric pH was also significantly higher when omeprazole and ranitidine were given in combination (pH 5.92 [IQR 4.75-6.46]) than either omeprazole alone (pH 4.88 [IQR 4.27-6.11], p=0.001) or ranitidine alone (pH 2.31 [IQR 2.04-5.27], p=0.0003). Likewise, the percentage of time that the gastric pH remained higher than 4 was significantly higher when omeprazole and ranitidine were given in combination (median 85.52%) than either omeprazole alone (74.31%, p=0.027) or ranitidine alone (27.94%, p=0.0002). CONCLUSION: When a PPI and H2 RA were administered concomitantly 30 minutes before breakfast, the H2 RA did not decrease the acid suppressive ability of the PPI; rather, it improved gastric acid control. Thus these results failed to support the initial hypothesis of this study. Further prospective studies are needed to test these findings in patients with gastroesophageal reflux disease as well as those with erosive esophagitis.

Prospective analysis of association between statin use and breast cancer risk in the women's health initiative.

BACKGROUND: Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Women's Health Initiative (WHI) to assess the relationship between statins and breast cancer risk. METHODS: The population included 154,587 postmenopausal women ages 50 to 79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD, 3.3) years. Information on statins was collected at baseline and years one, three, six, and nine. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided. RESULTS: Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus nonusers was 0.94 (95% CI, 0.83-1.06). In the multivariable-adjusted, time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71-1.07). There was no significant trend by overall duration of use (P value for trend 0.68). There was no effect of tumor stage, grade, or hormone receptor status. CONCLUSION: Overall, statins were not associated with breast cancer risk. IMPACT: Our study is one of the largest prospective observational studies on this topic, and substantially adds to the literature suggesting no relationship between statins and breast cancer risk.